Role of dynactin in endocytic traffic: Effects of dynamitin overexpression and colocalization with CLIP-170

Caterina Valetti, Dawn M. Wetzel, Michael Schrader, M. Josh Hasbani, Steven R. Gill, Thomas E. Kreis, Trina A. Schroer

Research output: Contribution to journalArticle

228 Scopus citations

Abstract

The flow of material from peripheral, early endosomes to late endosomes requires microtubules and is thought to be facilitated by the minus end- directed motor cytoplasmic dynein and its activator dynactin. The microtubule-binding protein CLIP-170 may also play a role by providing an early link to endosomes. Here, we show that perturbation of dynactin function in vivo affects endosome dynamics and trafficking. Endosome movement, which is normally bidirectional, is completely inhibited. Receptor-mediated uptake and recycling occur normally, but cells are less susceptible to infection by enveloped viruses that require delivery to late endosomes, and they show reduced accumulation of lysosomally targeted probes. Dynactin colocalizes at microtubule plus ends with CLIP-170 in a way that depends on CLIP-170's putative cargo-binding domain. Overexpression studies using p150(Glued), the microtubule-binding subunit of dynactin, and mutant and wild-type forms of CLIP-170 indicate that CLIP-170 recruits dynactin to microtubule ends. These data suggest a new model for the formation of motile complexes of endosomes and microtubules early in the endocytic pathway.

Original languageEnglish (US)
Pages (from-to)4107-4120
Number of pages14
JournalMolecular biology of the cell
Volume10
Issue number12
DOIs
StatePublished - Dec 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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